Ragaglitazar

Ragaglitazar.svg

Ragaglitazar is a thiazolidinedione and PPAR (peroxisome proliferator-activated receptor) agonist that was developed for the treatment of type 2 diabetes mellitus. It is a dual PPARα/γ agonist, meaning it activates both the PPARα and PPARγ receptors, which play a role in the regulation of glucose and lipid metabolism.

Mechanism of Action

Ragaglitazar functions by activating PPARα and PPARγ receptors.

• PPARα activation leads to increased fatty acid oxidation and improved lipid profiles, which can help reduce triglyceride levels and increase HDL cholesterol.
• PPARγ activation enhances insulin sensitivity, which helps in lowering blood glucose levels by improving the uptake of glucose in muscle and adipose tissue.

Development and Clinical Trials

Ragaglitazar was developed by Novo Nordisk, a pharmaceutical company known for its focus on diabetes care. During its development, Ragaglitazar showed promise in preclinical studies and early-phase clinical trials for its potential to improve both glycemic control and lipid profiles in patients with type 2 diabetes.

However, during later stages of clinical trials, concerns arose regarding the safety profile of Ragaglitazar. Specifically, there were findings of bladder cancer in animal studies, which raised significant safety concerns. As a result, the development of Ragaglitazar was halted, and it was never brought to market.

Safety Concerns

The primary safety concern that led to the discontinuation of Ragaglitazar was the potential risk of bladder cancer. This was observed in preclinical studies involving rodents, where an increased incidence of bladder tumors was noted. Although the exact mechanism by which Ragaglitazar might induce bladder cancer was not fully understood, the risk was deemed significant enough to outweigh the potential benefits of the drug.

Current Status

As of now, Ragaglitazar is not approved for use in any country, and its development has been discontinued. The case of Ragaglitazar highlights the importance of thorough safety evaluations in the drug development process, especially for chronic conditions like diabetes where long-term medication use is common.

Also see

• Thiazolidinedione
• PPAR agonist
• Type 2 diabetes mellitus
• Bladder cancer
• Drug development

PPAR Agonists
Type	Example
PPAR-α	Fibrate
PPAR-γ	Thiazolidinedione
PPAR-δ	GW501516
Dual/Triple Agonists
PPAR-α/γ	Saroglitazar
PPAR-α/δ	Elafibranor
PPAR-γ/δ	Tesaglitazar
PPAR pan	Bezafibrate